Protective Effect of Amyloid-β Peptides Against Herpes Simplex Virus-1 Infection in a Neuronal Cell Culture Model
Protective Effect of Amyloid-β Peptides Against Herpes Simplex Virus-1 Infection in a Neuronal Cell Culture Model
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DOI：
10.3233/jad-150652
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发表时间：
2016-01-01
影响因子：
4
通讯作者：
Fueloep, Tamas, Jr.
中科院分区：
文献类型：
--
作者：
Bourgade, Karine;Le Page, Aurelie;Fueloep, Tamas, Jr.
老年性淀粉样斑块是阿尔茨海默病（AD）的主要标志之一。它们与淀粉样肽（A β）的不溶性沉积相对应，并负责炎症反应和导致记忆丧失的神经变性。最近的数据表明，A β在体外具有抗菌和抗病毒活性。在这里，我们使用神经胶质瘤（H4）和胶质母细胞瘤（U118-MG）细胞共培养作为最小的体外模型来研究神经胶质瘤细胞是否产生a β，以及这是否会导致对HSV-1感染的保护性抗病毒活性。结果表明，H4细胞在HSV-1攻击时分泌A β (42)， U118-MG细胞能快速内化A β(42)。H4和U118-MG细胞在基础条件下产生促炎细胞因子TNF α和IL-1 α，但感染HSV-1的细胞没有显著上调其产生。两种细胞系都产生低水平的IFN α。然而，外来的A β(42)诱导了这些细胞因子的强烈产生。A β(42)和HSV-1的结合诱导了细胞系中促炎细胞因子TNF α、IL-1 β和IFN α的产生。在hsv -1感染的H4细胞的条件培养基（CM）转移实验中发现了A β(42)的抗病毒保护作用。在感染HSV-1的H4细胞的新生培养中，CM对HSV-1复制具有β依赖的保护作用。1型干扰素在这些试验中没有发挥作用。我们的数据证实，H4神经胶质瘤细胞对HSV-1感染产生A β(42)，从而抑制二次复制。这一机制可能在阿尔茨海默病的病因学中发挥作用。
Senile amyloid plaques are one of the main hallmarks of Alzheimer's disease (AD). They correspond to insoluble deposits of amyloid-beta peptides (A beta) and are responsible for the inflammatory response and neurodegeneration that lead to loss of memory. Recent data suggest that A beta possess antimicrobial and anti-viral activity in vitro. Here, we have used cocultures of neuroglioma (H4) and glioblastoma (U118-MG) cells as a minimal in vitro model to investigate whether A beta is produced by neuroglioma cells and whether this could result in protective anti-viral activity against HSV-1 infection. Results showed that H4 cells secreted A beta(42) in response to HSV-1 challenge and that U118-MG cells could rapidly internalize A beta(42). Production of pro-inflammatory cytokines TNF alpha and IL-1 alpha by H4 and U118-MG cells occurred under basal conditions but infection of the cells with HSV-1 did not significantly upregulate production. Both cell lines produced low levels of IFN alpha. However, extraneous A beta(42) induced strong production of these cytokines. A combination of A beta(42) and HSV-1 induced production of pro-inflammatory cytokines TNF alpha and IL-1 beta, and IFN alpha in the cell lines. The reported anti-viral protection of A beta(42) was revealed in transfer experiments involving conditioned medium (CM) of HSV-1-infected H4 cells. CM conferred A beta-dependent protection against HSV-1 replication in de novo cultures of H4 cells challenged with HSV-1. Type 1 interferons did not play a role in these assays. Our data established that H4 neuroglioma cells produced A beta(42) in response to HSV-1 infection thus inhibiting secondary replication. This mechanism may play a role in the etiology of AD.